It is the objective of the proposed research to characterize some of the molecular events which underly neuronal function and in so doing create a better understanding of the relationship between these biochemical processes, neurophysiological functions, and whole animal behavior. Doing this will involve using mutations to perturb normal nervous system function. The first approach is concerned with the attempt to understand the molecular defect underlying the neurophysiological and behavioral aberrations of temperature-sensitive paralytic mutants at the shibire locus. The second approach involves the isolation of mutants which are resistant to neurotropic drugs, and the screening of these mutants for associated behavioral defects. It is believed that mutants isolated in this way will be more yielding to biochemical analysis of the mutant molecular process. Two physiological processes will be investigated. The first being cholinergic transmission, while the other is the role played by cyclic nucleotides in nervous system function. The relationship that such mutants have with human neurological disorders, and their use as model systems is one possible application of these studies.